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A 64-year-old woman with long-standing seropositive rheumatoid arthritis presents with increasing fatigue and exertional dyspnoea over three months. She has no bleeding, no dietary change, and is post-menopausal. On examination she is pale with active synovitis of the metacarpophalangeal joints. Investigations: Hb 92 g/L, MCV 85 fL, reticulocytes 1.2 percent, serum iron low, TIBC low, ferritin 340 micrograms per litre, CRP 42 mg/L. Blood film: normocytic, normochromic red cells.
Questions
a) What is the most likely diagnosis, and which single iron-study feature best distinguishes it from iron deficiency? (2 marks)
Anaemia of chronic disease (anaemia of inflammation). The discriminator is the TIBC/transferrin: it is LOW in anaemia of chronic disease (alongside low iron and a normal or raised ferritin), whereas it is HIGH in iron deficiency. Ferritin is an acute-phase reactant and is normal or raised here, which also argues against pure iron deficiency.
b) Outline the pathophysiology in four steps. (3 marks)
- Chronic inflammation (rheumatoid arthritis) releases IL-6, which up-regulates hepatic hepcidin via JAK-STAT3.
- Hepcidin binds and degrades ferroportin on macrophages and duodenal enterocytes, trapping iron inside cells — a state of functional iron deficiency.
- Inflammatory cytokines (TNF-alpha, IFN-gamma) suppress erythropoiesis and blunt the erythropoietin response.
- A moderately shortened red-cell lifespan contributes, producing a hypoproliferative, normocytic anaemia.
c) List four causes of anaemia of chronic disease. (2 marks)
- Chronic infection (e.g. tuberculosis, osteomyelitis, HIV)
- Autoimmune disease (rheumatoid arthritis, inflammatory bowel disease, SLE)
- Malignancy
- Chronic kidney disease
- Chronic heart failure
d) Outline the management, naming one setting where oral iron alone is inadequate. (3 marks)
- Treat the underlying disease — the anaemia usually improves as inflammation settles.
- Iron: oral iron is often ineffective because hepcidin blocks absorption; intravenous iron is preferred when inflammation is active or coexisting deficiency is present (this is the setting where oral iron alone is inadequate).
- Erythropoiesis-stimulating agents for CKD-related and chemotherapy-induced anaemia, titrated to a modest Hb target (around 100 to 115 g/L).
- Transfusion reserved for symptomatic or severe anaemia only.